WO2013094683A1 - Composition for skin containing silicone base - Google Patents

Composition for skin containing silicone base Download PDF

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Publication number
WO2013094683A1
WO2013094683A1 PCT/JP2012/083063 JP2012083063W WO2013094683A1 WO 2013094683 A1 WO2013094683 A1 WO 2013094683A1 JP 2012083063 W JP2012083063 W JP 2012083063W WO 2013094683 A1 WO2013094683 A1 WO 2013094683A1
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WO
WIPO (PCT)
Prior art keywords
composition
silicone
skin
silicone base
weight
Prior art date
Application number
PCT/JP2012/083063
Other languages
French (fr)
Japanese (ja)
Inventor
栄次郎 堀沢
伊原　幹人
Original Assignee
マルホ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by マルホ株式会社 filed Critical マルホ株式会社
Priority to US14/362,198 priority Critical patent/US20140357729A1/en
Priority to EP12858836.5A priority patent/EP2796149A4/en
Priority to CN201280063022.1A priority patent/CN103998062A/en
Publication of WO2013094683A1 publication Critical patent/WO2013094683A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
    • A61K8/585—Organosilicon compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/89—Polysiloxanes
    • A61K8/891—Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18

Definitions

  • the present invention relates to a skin composition containing a silicone base. More specifically, the present invention relates to an anhydrous dermatological composition containing a silicone base and containing an active ingredient in a dispersed or dissolved state.
  • the skin composition is required to have a high potency of the active ingredient (active ingredient), that is, the stability of the active ingredient and excellent percutaneous absorption, but another important characteristic is that when applied to the skin It is required to be excellent in touch and feel.
  • active ingredient active ingredient
  • an ointment is a dosage form with excellent coating properties, but it is accompanied by a sticky feeling, and therefore, it is required to have a light and smooth touch (texture) with reduced stickiness.
  • Patent Document 1 discloses an anhydrous drug having a combination of at least one active ingredient and a silicone agent containing at least one organopolysiloxane elastomer not containing a hydrophilic group.
  • a composition is disclosed in which the active ingredient is present in dissolved form in the composition. According to Patent Document 1, it is said that the composition can give a soft feel while having no stickiness, oiliness, and a shining effect.
  • composition of patent document 1 contains the active ingredient in the form which melt
  • a solvent-soluble composition is prepared by dispersing droplets of an aqueous solvent in which an active ingredient is dissolved in a silicone agent.
  • the use of a non-silicone thickener thickener without silicon
  • the composition of patent document 1 contains only about 70 weight% of silicone agents and there are many other component amounts, there exists a problem that the outstanding touch and the usability
  • the present inventors have repeatedly investigated the base of the composition used for the skin, and as a result, by combining a specific silicone agent as the base, the skin composition excellent in feel and use feeling We succeeded in obtaining the product and completed the present invention.
  • the present invention capable of solving the above problems is an anhydrous skin composition
  • (A) 80% by weight or more of the composition is a silicone base
  • the silicone base is (B1) Silicone elastomer,
  • (B2) comprising a cyclic volatile methylsiloxane having 3 to 6 silicon atoms, and (b3) a linear dimethylpolysiloxane and / or a linear methylphenylpolysiloxane
  • C) contains an active ingredient present in a dispersed or dissolved form in the composition, and (D) does not contain a non-silicone thickener.
  • the above composition contains, as a base, a silicone elastomer (b1) excellent in feel and usability, and is a cyclic solvent having 3 to 6 silicon atoms as an adjusting solvent for diluting the silicone elastomer and adjusting the viscosity.
  • a silicone base comprising the above (b1) to (b3) Since it accounts for 80% by weight or more of the composition, the feel and feeling of use are very excellent. Moreover, since a non-silicone thickener is not contained, a touch and a usability are not impaired.
  • the composition preferably contains 83% by weight or more of the silicone base, and the silicone base preferably comprises only (b1) to (b3).
  • the composition contains the active ingredient in a dispersed form
  • composition according to the present invention contains a silicone base comprising three specific components and has a high blending ratio, the feel to the skin and the feeling of use are very excellent.
  • silicone elastomer (b1) As preferable examples of the silicone elastomer (b1) according to the present invention, as disclosed in JP-A-11-222556 (EP0915120; US5929164), (A) Polysiloxane containing ⁇ Si—H of formula R3SiO (R′2SiO) a (R ′′ HSiO) bSiR3 and optionally polysiloxane containing ⁇ Si—H of formula HR2SiO (R′2SiO) cSiR2H or HR2SiO (R′2SiO) a (R ′′ HSiO) bSiR2H ⁇ Si—H-containing polysiloxane (wherein R, R ′ and R ′′ are alkyl groups having 1 to 6 carbon atoms; a is 0 ⁇ 250; b is 1 to 250; c is 0 to 250); (B) Alkene; (C) a platinum group metal catalyst; and (
  • Examples of the cyclic volatile methylsiloxane (b2) having 3 to 6 silicon atoms according to the present invention include hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexasiloxane. Particularly preferred is decamethylcyclopentasiloxane.
  • linear dimethylpolysiloxane (b3) examples include those having a silicon atom number in the range of 5 to 652 and a viscosity in the range of 2 to 5000 mm 2 / s. Such a linear dimethylpolysiloxane is commercially available, and can be obtained from, for example, Dow Corning.
  • linear methylphenyl polysiloxane (b3) according to the present invention examples include those having the number of silicon atoms in the range of 3 to 412 and the viscosity in the range of 10 to 1000 mm 2 / s. .
  • Such a linear methylphenyl polysiloxane is commercially available, and can be obtained from, for example, Dow Corning.
  • linear dimethylpolysiloxane is more preferred.
  • the silicone base according to the present invention may further contain other silicone agents.
  • other silicone agents linear methyl hydrogen polysiloxane or the like can be used.
  • modified polysiloxanes with organic groups introduced into the side chain and terminal (alcohol modification, alkyl modification, aralkyl modification, polyether modification, fatty acid ester modification, amino modification, epoxy modification, carboxyl modification, methacryl modification) can also be used. is there.
  • the blending ratio of the other silicone agent in the silicone base according to the present invention is preferably 10% by weight or less, more preferably 5% by weight or less, and further preferably 3% by weight or less.
  • a particularly preferred silicone base according to the present invention does not contain other silicone agents and consists only of (b1) to (b3).
  • the active ingredient contained in the composition according to the present invention may be hydrophilic or lipophilic (lipid-soluble).
  • Preferred active ingredients in the composition according to the present invention include steroids, immunosuppressive substances, anticancer agents, trace active substances (for example, active vitamin D 3 , antibiotics, antibacterial agents, steroidal or nonsteroidal antiinflammatory agents, opioids Drugs, natural organic compounds, terpenes, etc.), but are not limited thereto.
  • the composition according to the present invention may contain two or more active ingredients.
  • the active ingredient may be present in a dispersed form (drug-dispersed) in the composition, may be present in a dissolved form (drug-dissolved), partly dispersed, and the rest It may exist in a dissolved form (partially dispersed).
  • Whether the active ingredient exists in a dispersed form or a dissolved form can be determined by whether or not the dispersion of crystals is observed with a microscope.
  • An appropriate blending ratio of the active ingredient in the composition cannot be generally specified because it varies depending on the type of the active ingredient, but generally it is in the range of 0.001 to 5% by weight. In the case of active substances with high pharmacological effects (steroids, immunosuppressive substances, trace active substances, etc.), the range of 0.001 to 0.5% by weight is more appropriate. What is necessary is just to adjust suitably the application quantity and application frequency to the skin of the composition which concerns on this invention according to the skin symptom and the active ingredient in a composition.
  • 86: 3 to 55 is preferable
  • the viscosity of the composition is preferably in the range of 10 to 100,000 mPa ⁇ s
  • the weight ratio of (b1) to (b3) in the silicone base is set so that the composition has a viscosity in the above range. You may adjust.
  • the measurement temperature is 25 ° C.
  • the rotation speed is 20 rpm
  • the measurement time is 30 seconds with a B-type viscometer [TVB-10H, rotor: No. 7].
  • the composition is a low-viscosity composition that is almost liquid, use a B-type viscometer [TVB-10H, rotor: HH-12] at a measurement temperature of 25 ° C., a rotation speed of 50 rpm, and a measurement time of 10 seconds. It can be measured.
  • the more preferred viscosity of the composition is 100 to 50,000 mPa ⁇ s for the drug-dispersed composition and 1,000 to 50,000 mPa ⁇ s for the drug-dissolved composition.
  • the blending ratio of the silicone elastomer (b1) increases, the viscosity increases, and when the blending ratio of the cyclic volatile methylsiloxane (b2) and the linear dimethylpolysiloxane / linear methylphenylpolysiloxane (b3) is increased, Viscosity decreases.
  • the viscosity can be finely adjusted by appropriately adjusting the ratio between the cyclic volatile methylsiloxane (b2) and the linear dimethylpolysiloxane / linear methylphenylpolysiloxane (b3).
  • the base (excluding the active ingredient from the composition) is the silicone group. It can be prepared without using other base ingredients, but it can be blended into normal skin compositions such as dyes, fragrances, pigments, antioxidants, and UV absorbers as necessary. Ingredients may be used.
  • the blending ratio of the silicone base in the composition is preferably 93% by weight or more, more preferably 96% by weight or more, and 98% by weight. % Or more is particularly preferable.
  • a composition drug-dissolving composition
  • an oily solvent also called non-aqueous solvent or oily base
  • a surfactant or a non-silicone thickener for example, a paste-like or solid hydrocarbon such as wax is added.
  • a drug-soluble composition can be obtained without using a base thickener or the like.
  • a drug-dissolving composition is prepared even if these are not included. be able to.
  • the proportion of the silicone base in the composition is preferably 85% by weight or more, more preferably 88% by weight or more, and 93% by weight. % Or more is particularly preferable.
  • oily solvent used for dissolving the lipophilic active ingredient examples include fatty acids, fatty acid esters, higher alcohols, hydrocarbons and the like. Particularly preferred oily solvents are diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, medium chain triglyceride, propylene glycol fatty acid ester, glycerin triisooctanoate, isostearic acid, hexyl decanol, oleyl alcohol, isostearyl alcohol, octyldodecanol, palmitic Isopropyl acid, isopropyl myristate, cetyl 2-ethylhexanoate, octyldodecyl myristate, hexadecyl isostearate, isostearyl palmitate, oleyl oleate, refined jojoba oil, squalane, liquid paraffin, light liquid par
  • the composition according to the present invention is an anhydrous composition and essentially does not contain water.
  • “essentially not contained” means that it is not intentionally added to the composition, and means that it is inevitably included only when it is mixed into the composition.
  • the composition according to the present invention essentially does not contain an aqueous component (such as a lower alcohol or a polyhydric alcohol) or contains only a small amount. That is, the composition according to the present invention is contained only when it is inevitably mixed.
  • Usually less than 1% by weight and the total amount of the aqueous component is 5% by weight or less, preferably 3% by weight or less of the composition. More preferably, it is a composition of 1% by weight or less, particularly preferably a composition containing no water, and more preferably a composition containing no water or an aqueous component.
  • compositions according to the present invention include gel-to-liquid dosage forms such as ointment-like oily gels to lotions.
  • composition according to the present invention may contain components blended in a normal skin composition, such as a dye, a fragrance, a pigment, an antioxidant, and an ultraviolet absorber, if necessary.
  • a dye such as a dye, a fragrance, a pigment, an antioxidant, and an ultraviolet absorber
  • the proportion of these additive components in the composition is preferably 10% by weight or less, more preferably 3% by weight or less, and particularly preferably 1% by weight or less.
  • the external preparation of the present invention includes a composition obtained by arbitrarily combining these. Also included are compositions obtained by arbitrarily combining the concentration ranges described for each component.
  • numerical ranges such as concentration and viscosity described in the preceding paragraph can be arbitrarily combined, and when a plurality of numerical ranges are described, an upper limit value or a lower limit value of each numerical range can be arbitrarily combined.
  • composition according to the present invention is a drug-dispersed type, by adding (b3) to the premixed mixture of (b1) and (b2) and stirring, or (b1), (b2) and A method of preparing the mixture (b1 to b3) by adding (b3) and stirring and then dispersing the active ingredient with a homomixer can be mentioned.
  • composition according to the present invention is a drug-dissolving type, by adding (b3) to the premixed mixture of (b1) and (b2) and stirring, or (b1), (b2) and There is a method in which (b1 to b3) mixture is prepared by adding (b3) and stirring, and then the active ingredient previously dissolved in an oily solvent is stirred and mixed.
  • the composition obtained by the above production process can be adjusted from semi-solid to liquid by adjusting the blending ratio of (b1) to (b3). More specifically, an ointment-like semi-solid composition can be obtained by reducing the amount of (b2) and / or (b3), and the amount of (b2) and / or (b3) is increased. Thus, a lotion-like composition can be obtained.
  • composition having the composition shown in Tables 1 and 2 was prepared by the following procedure.
  • active ingredients steroids (betamethasone butyrate propionate) and activated VD 3 (maxacalcitol) were used.
  • Method for preparing drug-dispersed composition (1) Weigh the mixture of (b1) and (b2) into a suitable container. (2) Add (b3) to (1) and mix. (3) Add the active ingredient to (2) and stir with a homomixer (6000 rpm, 5 minutes) at room temperature to disperse.
  • composition prepared as described above was a white translucent gel-like liquid composition.
  • dispersion of crystals was confirmed, and the composition was confirmed to be a drug-dispersed composition.
  • each composition was evaluated on the basis of whether it had little smoothness and smooth touch by apply
  • the number of subjects is four, and each subject is evaluated for each composition as ⁇ , ⁇ for good, ⁇ for general, ⁇ for poor, and ⁇ for the average of four subjects.
  • Each composition was evaluated.
  • the compositions shown in Tables 1 and 2 showed higher viscosity as the blending ratio of the silicone elastomer (b1) was larger.
  • the compositions No. 007 and No. 009 to No. 011 were measured under the measurement conditions for low viscosity (condition 1), and the composition No. 002 was measured under the measurement conditions for high viscosity (condition 2). ).
  • Example 2 Preparation of drug-soluble composition
  • a composition having the composition shown in Tables 3 and 4 was prepared by the following procedure.
  • the active ingredient, a mixture of silicone elastomer (b1) and cyclic volatile methylsiloxane [decamethylcyclopentasiloxane] (b2), and linear dimethylpolysiloxane (b3) are the same as those used in Example 1, and sebacin NIKKOL DES-SP from Nikko Chemicals was used as the diethyl acid.
  • Method for preparing drug-dissolving composition (1) Weigh the mixture of (b1) and (b2) into a suitable container. (2) Add (b3) to (1) and mix. (3) Add the active ingredient previously dissolved in the oily solvent to (2), stir with a homomixer (6000 rpm, 5 minutes) at room temperature and mix.
  • the composition prepared as described above was a white translucent gel to liquid composition.
  • the dispersion of crystals was not confirmed, and it was confirmed to be a drug-dissolving composition.
  • the compositions shown in Tables 3 and 4 showed higher viscosity as the blending ratio of the silicone elastomer (b1) was larger.
  • the touch (hand) was evaluated by the same method as Example 1, and the viscosity was measured about the composition of No.102, No.105, No.107, No.108, No.111.
  • the compositions of No. 105, No. 107, No. 108, and No. 111 were measured under the above condition 1, and the composition of No. 102 was measured under the above condition 2.
  • the results are shown in Table 3.

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Abstract

The present invention addresses the problem of providing a composition for the skin, which has excellent texture and feeling of use. The present invention provides an anhydrous composition for the skin, which is characterized in that: (A) 80% by weight or more of the composition is composed of a silicone base; (B) the silicone base contains (b1) a silicone elastomer, (b2) a cyclic volatile methyl siloxane that has 3-6 silicon atoms and (b3) a linear dimethyl polysiloxane and/or a linear methylphenyl polysiloxane; (C) the composition contains an active component that is present in a dispersed or dissolved state; and (D) the composition does not contain a non-silicone thickener.

Description

シリコーン基剤を含有する皮膚用組成物Dermal composition containing a silicone base
　本発明は、シリコーン基剤を含有する皮膚用組成物に関する。より詳しくは、シリコーン基剤を含有し、主薬を分散した状態もしくは溶解した状態で含有する無水の皮膚用組成物に関する。 The present invention relates to a skin composition containing a silicone base. More specifically, the present invention relates to an anhydrous dermatological composition containing a silicone base and containing an active ingredient in a dispersed or dissolved state.
　皮膚に使用するための外用剤として、従来から様々な剤型の組成物が使用されている。皮膚用組成物には、主薬（活性成分）の効き目が高いこと、すなわち、主薬の安定性や経皮吸収性に優れることが求められるが、別の重要な特性として、皮膚に塗布したときの感触や使用感に優れることが要求される。特に、軟膏剤は被覆性に優れる剤型であるが、べたつき感が伴うことから、べたつき感を抑えた軽い滑らかな感触（肌触り）であることが要求される。 As a topical preparation for use on the skin, various types of compositions have been conventionally used. The skin composition is required to have a high potency of the active ingredient (active ingredient), that is, the stability of the active ingredient and excellent percutaneous absorption, but another important characteristic is that when applied to the skin It is required to be excellent in touch and feel. In particular, an ointment is a dosage form with excellent coating properties, but it is accompanied by a sticky feeling, and therefore, it is required to have a light and smooth touch (texture) with reduced stickiness.
　感触や使用感に優れた組成物として、例えば、特許文献１には、少なくとも１の活性成分、及び親水性基を含まない少なくとも１のオルガノポリシロキサンエラストマーを含むシリコーン剤を組み合わせて有する無水の薬剤組成物において、前記活性成分が前記組成物中に溶解された形態で存在する組成物が開示されている。特許文献１によれば、当該組成物は、べた付き、油っこい、及びてかり効果がない一方で、柔らかな感触を与えることができるとされている。 As a composition excellent in touch and use feeling, for example, Patent Document 1 discloses an anhydrous drug having a combination of at least one active ingredient and a silicone agent containing at least one organopolysiloxane elastomer not containing a hydrophilic group. In a composition, a composition is disclosed in which the active ingredient is present in dissolved form in the composition. According to Patent Document 1, it is said that the composition can give a soft feel while having no stickiness, oiliness, and a shining effect.
　特許文献１の組成物は、活性成分を溶解した形態で含むものであるが、活性成分はシリコーン剤に溶解しないため、活性成分を溶解するための溶剤として、水性の溶剤（無水エタノール等のアルコールタイプの溶媒等）を使用し、活性成分を溶解した水性溶剤の液滴をシリコーン剤に分散することにより、薬物溶解型の組成物を調製している。
　水性溶剤をシリコーン剤に分散するためには、非シリコーン性増粘剤（ケイ素を有さない増粘剤）の使用が必須となるが、増粘剤の添加は、組成物を皮膚に塗布した際の感触を悪化させる原因となる。
　また、特許文献１の組成物は、シリコーン剤を約70重量％しか含まず、他の成分量が多いため、シリコーン剤の特性である優れた感触や使用感が損なわれるという問題がある。 Although the composition of patent document 1 contains the active ingredient in the form which melt | dissolved, since an active ingredient does not melt | dissolve in a silicone agent, as a solvent for melt | dissolving an active ingredient, it is an aqueous solvent (alcohol type, such as absolute ethanol). A solvent-soluble composition is prepared by dispersing droplets of an aqueous solvent in which an active ingredient is dissolved in a silicone agent.
In order to disperse the aqueous solvent in the silicone agent, the use of a non-silicone thickener (thickener without silicon) is essential, but the addition of the thickener applied the composition to the skin. It may cause a worse feeling.
Moreover, since the composition of patent document 1 contains only about 70 weight% of silicone agents and there are many other component amounts, there exists a problem that the outstanding touch and the usability | use feeling which are the characteristics of a silicone agent are impaired.
特開2007-530515号公報JP 2007-530515 A
　したがって、現在もなお、より優れた感触や使用感を有する皮膚用組成物を開発することが望まれている。 Therefore, it is still desired to develop a dermatological composition that has a better feel and feel.
　本発明者らは、上記状況に鑑み、皮膚に使用する組成物の基剤について検討を繰り返した結果、基剤として特定のシリコーン剤を組合せることにより、感触や使用感に優れた皮膚用組成物を得ることに成功し、本発明を完成した。 In view of the above situation, the present inventors have repeatedly investigated the base of the composition used for the skin, and as a result, by combining a specific silicone agent as the base, the skin composition excellent in feel and use feeling We succeeded in obtaining the product and completed the present invention.
　上記課題を解決可能な本発明は、無水の皮膚用組成物であって、
（A）組成物の80重量％以上がシリコーン基剤であること、
（B）前記シリコーン基剤が、
　（b1）シリコーンエラストマー、
　（b2）ケイ素原子数3～6の環状揮発性メチルシロキサン、および
　（b3）直鎖型ジメチルポリシロキサン及び／又は直鎖型メチルフェニルポリシロキサン
　を含んでなること、
（C）組成物中に分散もしくは溶解した形態で存在する活性成分を含むこと、および
（D）非シリコーン性増粘剤を含有しないこと
を特徴とする。 The present invention capable of solving the above problems is an anhydrous skin composition,
(A) 80% by weight or more of the composition is a silicone base,
(B) the silicone base is
(B1) Silicone elastomer,
(B2) comprising a cyclic volatile methylsiloxane having 3 to 6 silicon atoms, and (b3) a linear dimethylpolysiloxane and / or a linear methylphenylpolysiloxane,
(C) contains an active ingredient present in a dispersed or dissolved form in the composition, and (D) does not contain a non-silicone thickener.
　上記組成物は、基剤として、感触と使用感に優れたシリコーンエラストマー（b1）を含み、且つ、シリコーンエラストマーを希釈し、粘度を調節するための調節溶媒として、ケイ素原子数3～6の環状揮発性メチルシロキサン（b2）と、直鎖型ジメチルポリシロキサン及び／又は直鎖型メチルフェニルポリシロキサン（b3）を含むことに加え、前記（b1）～（b3）を含んでなるシリコーン基剤が組成物の80重量％以上を占めることから、感触および使用感が非常に優れている。
　また、非シリコーン性増粘剤を含有しないため、感触や使用感が損なわれることがない。 The above composition contains, as a base, a silicone elastomer (b1) excellent in feel and usability, and is a cyclic solvent having 3 to 6 silicon atoms as an adjusting solvent for diluting the silicone elastomer and adjusting the viscosity. In addition to containing volatile methylsiloxane (b2) and linear dimethylpolysiloxane and / or linear methylphenylpolysiloxane (b3), a silicone base comprising the above (b1) to (b3) Since it accounts for 80% by weight or more of the composition, the feel and feeling of use are very excellent.
Moreover, since a non-silicone thickener is not contained, a touch and a usability are not impaired.
　前記組成物は、前記シリコーン基剤を83重量％以上含むことが好ましく、また、前記シリコーン基剤は、前記（b1）～（b3）のみからなることが好ましい。 The composition preferably contains 83% by weight or more of the silicone base, and the silicone base preferably comprises only (b1) to (b3).
　前記組成物が、前記活性成分を分散した形態で含む場合は、前記組成物の93重量％以上が前記シリコーン基剤であることが好ましく、また、前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝5.5～11.5：40～86：3～55（ただし、b1＋b2＋b3＝100とする。以下同じ）であることが好ましく、b1：b2：b3＝8～11.5：55～86：3～35であることがより好ましい。 When the composition contains the active ingredient in a dispersed form, 93% by weight or more of the composition is preferably the silicone base, and (b1) to (b3) in the silicone base Is preferably b1: b2: b3 = 5.5 to 11.5: 40 to 86: 3 to 55 (provided that b1 + b2 + b3 = 100, the same shall apply hereinafter), and b1: b2: b3 = 8 to 11.5: It is more preferably 55 to 86: 3 to 35.
　前記組成物が、前記活性成分を溶解した形態で含む場合は、前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝10～11.5：73～85：3～17（ただし、b1＋b2＋b3＝100とする。以下同じ）であることが好ましく、b1：b2：b3＝10.7～11.5：78～85：3～11.5であることがより好ましい。 When the composition contains the active ingredient in a dissolved form, the weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 10 to 11.5: 73 to 85: 3 to 17 (provided that b1 + b2 + b3 = 100; the same applies hereinafter), and more preferably b1: b2: b3 = 10.7 to 11.5: 78 to 85: 3 to 11.5.
　本発明に係る組成物は、特定の３成分を含んでなるシリコーン基剤を含み、かつその配合割合が高いため、皮膚への感触や使用感が非常に優れている。 Since the composition according to the present invention contains a silicone base comprising three specific components and has a high blending ratio, the feel to the skin and the feeling of use are very excellent.
　本発明に係るシリコーンエラストマー（b1）の好ましい例としては、特開平11－222556号（EP0915120；US5929164）に開示されているように、
（A）式R3SiO（R′2SiO）a（R″HSiO）bSiR3の≡Si-Hを含有するポリシロキサン及び任意に式HR2SiO（R′2SiO）cSiR2Hの≡Si－Hを含有するポリシロキサン又はHR2SiO（R′2SiO）a（R″HSiO）bSiR2Hの≡Si－Hを含有するポリシロキサン（式中のR，R′及びR″は炭素原子数が1～6のアルキル基であり；aは0～250；bは1～250；cは0～250である）；
（B）アルケン；
（C）白金族金属触媒；及び
（D）溶媒化合物
をシリコーンエラストマーが前記アルケンにおける二重結合にまたがる≡Si－Hの架橋及び付加によって形成されるまで、混合及び反応させる工程からなることを特徴とする、シリコーンエラストマーの製造法
によって製造されたシリコーンエラストマーを挙げることができる。これらのエラストマーとしては、市販されているものが利用可能であり、例えばダウコーニング社から入手できる。 As preferable examples of the silicone elastomer (b1) according to the present invention, as disclosed in JP-A-11-222556 (EP0915120; US5929164),
(A) Polysiloxane containing ≡Si—H of formula R3SiO (R′2SiO) a (R ″ HSiO) bSiR3 and optionally polysiloxane containing ≡Si—H of formula HR2SiO (R′2SiO) cSiR2H or HR2SiO (R′2SiO) a (R ″ HSiO) bSiR2H≡Si—H-containing polysiloxane (wherein R, R ′ and R ″ are alkyl groups having 1 to 6 carbon atoms; a is 0 ~ 250; b is 1 to 250; c is 0 to 250);
(B) Alkene;
(C) a platinum group metal catalyst; and (D) a solvent compound is mixed and reacted until the silicone elastomer is formed by crosslinking and addition of ≡Si—H across the double bond in the alkene. And a silicone elastomer produced by a method for producing a silicone elastomer. As these elastomers, commercially available ones can be used, for example, available from Dow Corning.
　本発明に係るケイ素原子数3～6の環状揮発性メチルシロキサン（b2）としては、ヘキサメチルシクロトリシロキサン、オクタメチルシクロテトラシロキサン、デカメチルシクロペンタシロキサン、及びドデカメチルシクロヘキサシロキサンが挙げられる。特に好ましくは、デカメチルシクロペンタシロキサンである。 Examples of the cyclic volatile methylsiloxane (b2) having 3 to 6 silicon atoms according to the present invention include hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexasiloxane. Particularly preferred is decamethylcyclopentasiloxane.
　本発明に係る直鎖型ジメチルポリシロキサン（b3）としては、ケイ素原子数が5～652の範囲にあり、粘度が2～5000 mm2／sの範囲にあるものを挙げることができる。このような直鎖型ジメチルポリシロキサンは、市販されているものが利用可能であり、例えばダウコーニング社から入手できる。
　また、本発明に係る直鎖型メチルフェニルポリシロキサン（b3）としては、ケイ素原子数が3～412の範囲にあり、粘度が10～1000 mm2／sの範囲にあるものを挙げることができる。このような直鎖型メチルフェニルポリシロキサンは、市販されているものが利用可能であり、例えばダウコーニング社から入手できる。
　本発明の（b3）としては、直鎖型ジメチルポリシロキサンがより好ましい。 Examples of the linear dimethylpolysiloxane (b3) according to the present invention include those having a silicon atom number in the range of 5 to 652 and a viscosity in the range of 2 to 5000 mm 2 / s. Such a linear dimethylpolysiloxane is commercially available, and can be obtained from, for example, Dow Corning.
Examples of the linear methylphenyl polysiloxane (b3) according to the present invention include those having the number of silicon atoms in the range of 3 to 412 and the viscosity in the range of 10 to 1000 mm 2 / s. . Such a linear methylphenyl polysiloxane is commercially available, and can be obtained from, for example, Dow Corning.
As (b3) of the present invention, linear dimethylpolysiloxane is more preferred.
　本発明に係るシリコーン基剤は、上記（b1）～（b3）に加えて、さらに、他のシリコーン剤を含んでもよい。他のシリコーン剤として、直鎖型のメチルハイドロジェンポリシロキサン等が利用可能である。さらに、側鎖、末端に有機基を導入した変性型ポリシロキサン（アルコール変性、アルキル変性、アラルキル変性、ポリエーテル変性、脂肪酸エステル変性、アミノ変性、エポキシ変性、カルボキシル変性、メタクリル変性）も利用可能である。
　本発明に係るシリコーン基剤における他のシリコーン剤の配合割合は、10重量％以下であることが好ましく、5重量％以下であることがより好まく、3重量％以下であることがさらに好ましい。特に好ましい本発明に係るシリコーン基剤は、他のシリコーン剤を含まず、（b1）～（b3）のみからなる。 In addition to the above (b1) to (b3), the silicone base according to the present invention may further contain other silicone agents. As another silicone agent, linear methyl hydrogen polysiloxane or the like can be used. In addition, modified polysiloxanes with organic groups introduced into the side chain and terminal (alcohol modification, alkyl modification, aralkyl modification, polyether modification, fatty acid ester modification, amino modification, epoxy modification, carboxyl modification, methacryl modification) can also be used. is there.
The blending ratio of the other silicone agent in the silicone base according to the present invention is preferably 10% by weight or less, more preferably 5% by weight or less, and further preferably 3% by weight or less. A particularly preferred silicone base according to the present invention does not contain other silicone agents and consists only of (b1) to (b3).
　本発明に係る組成物中に含まれる活性成分は、親水性であっても親油性（脂溶性）であってもよい。本発明に係る組成物における好ましい活性成分として、ステロイド、免疫抑制物質、抗癌剤、微量活性物質（例えば、活性型ビタミンD３、抗生物質、抗菌剤、ステロイド系又は非ステロイド系抗炎症剤、オピオイド系薬物、天然有機化合物、テルペン類等）を挙げることができるが、これらに限定される訳ではない。さらに本発明に係る組成物は上記活性成分２種以上を含有することができる。
　前記活性成分は、前記組成物中に分散した形態（薬物分散型）で存在していてもよく、溶解した形態（薬物溶解型）で存在していてもよく、一部が分散し、残りが溶解した形態（一部分散型）で存在していてもよい。活性成分が分散した形態で存在するか溶解した形態で存在するかは、顕微鏡で結晶の分散が観察されるか否かによって判断することができる。
　組成物中の活性成分の適切な配合割合は、活性成分の種類によっても異なるため一概には言えないが、一般的に0.001～5重量％の範囲が適切である。薬理効果の高い活性物質（ステロイド、免疫抑制物質、微量活性物質等）の場合、0.001～0.5重量％の範囲がより適切である。
　本発明に係る組成物の皮膚への塗布量・塗布頻度は、皮膚の症状や組成物中の活性成分に応じて適宜調節すればよい。 The active ingredient contained in the composition according to the present invention may be hydrophilic or lipophilic (lipid-soluble). Preferred active ingredients in the composition according to the present invention include steroids, immunosuppressive substances, anticancer agents, trace active substances (for example, active vitamin D 3 , antibiotics, antibacterial agents, steroidal or nonsteroidal antiinflammatory agents, opioids Drugs, natural organic compounds, terpenes, etc.), but are not limited thereto. Furthermore, the composition according to the present invention may contain two or more active ingredients.
The active ingredient may be present in a dispersed form (drug-dispersed) in the composition, may be present in a dissolved form (drug-dissolved), partly dispersed, and the rest It may exist in a dissolved form (partially dispersed). Whether the active ingredient exists in a dispersed form or a dissolved form can be determined by whether or not the dispersion of crystals is observed with a microscope.
An appropriate blending ratio of the active ingredient in the composition cannot be generally specified because it varies depending on the type of the active ingredient, but generally it is in the range of 0.001 to 5% by weight. In the case of active substances with high pharmacological effects (steroids, immunosuppressive substances, trace active substances, etc.), the range of 0.001 to 0.5% by weight is more appropriate.
What is necessary is just to adjust suitably the application quantity and application frequency to the skin of the composition which concerns on this invention according to the skin symptom and the active ingredient in a composition.
　前記シリコーン基剤における（b1）～（b3）の重量比率は、前記組成物が薬物分散型の組成物（一部分散型を含む）である場合は、b1：b2：b3＝5.5～11.5：40～86：3～55であることが好ましく、b1：b2：b3＝8～11.5：55～86：3～35であることがより好ましく、b1：b2：b3＝8．2～11.5：60～84：4～32であることが特に好ましい。
　薬物溶解型の組成物である場合は、b1：b2：b3＝10～11.5：73～85：3～17であることが好ましく、b1：b2：b3＝10.7～11.5：78～85：3～11.5であることがより好ましく、b1：b2：b3＝10.7～11.5：78～84：4～11.3であることが特に好ましい。
　また、組成物の粘度が、10～100,000 mPa・sの範囲にあることが好ましいため、組成物が前記範囲の粘度を持つように、シリコーン基剤における（b1）～（b3）の重量比率を調節してもよい。上記粘度は、組成物がゲル状に近い高粘度組成物の場合は、B型粘度計[TVB-10H、ローター：No.7]にて、測定温度25℃、回転数20rpm、測定時間30秒で測定でき、組成物が液状に近い低粘度組成物の場合は、B型粘度計[TVB-10H、ローター：HH-12]にて、測定温度25℃、回転数50rpm、測定時間10秒で測定できる。組成物のより好ましい粘度は、薬物分散型組成物の場合は100～50,000 mPa・sであり、薬物溶解型組成物の場合は、1,000～50,000mPa・sである。シリコーンエラストマー（b1）の配合割合が高くなると粘度が高くなり、環状揮発性メチルシロキサン（b2）や、直鎖型ジメチルポリシロキサン・直鎖型メチルフェニルポリシロキサン（b3）の配合割合を高くすると、粘度が低くなる。また、環状揮発性メチルシロキサン（b2）と、直鎖型ジメチルポリシロキサン・直鎖型メチルフェニルポリシロキサン（b3）との割合を適宜調整することにより、粘度の微調整が可能になる。 The weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 5.5 to 11.5: 40 when the composition is a drug-dispersed composition (including a partially dispersed composition). 86: 3 to 55 is preferable, b1: b2: b3 = 8 to 11.5: 55 to 86: 3 to 35 is more preferable, and b1: b2: b3 = 8.2 to 11.5: 60 to 84: 4 to 32 is particularly preferable.
In the case of a drug-dissolving composition, b1: b2: b3 = 10 to 11.5: 73 to 85: 3 to 17 is preferable, and b1: b2: b3 = 10.7 to 11.5: 78 to 85: 3 to 11.5 is more preferable, and b1: b2: b3 = 10.7 to 11.5: 78 to 84: 4 to 11.3 is particularly preferable.
Further, since the viscosity of the composition is preferably in the range of 10 to 100,000 mPa · s, the weight ratio of (b1) to (b3) in the silicone base is set so that the composition has a viscosity in the above range. You may adjust. When the composition is a high-viscosity composition close to a gel, the measurement temperature is 25 ° C., the rotation speed is 20 rpm, and the measurement time is 30 seconds with a B-type viscometer [TVB-10H, rotor: No. 7]. If the composition is a low-viscosity composition that is almost liquid, use a B-type viscometer [TVB-10H, rotor: HH-12] at a measurement temperature of 25 ° C., a rotation speed of 50 rpm, and a measurement time of 10 seconds. It can be measured. The more preferred viscosity of the composition is 100 to 50,000 mPa · s for the drug-dispersed composition and 1,000 to 50,000 mPa · s for the drug-dissolved composition. When the blending ratio of the silicone elastomer (b1) increases, the viscosity increases, and when the blending ratio of the cyclic volatile methylsiloxane (b2) and the linear dimethylpolysiloxane / linear methylphenylpolysiloxane (b3) is increased, Viscosity decreases. Further, the viscosity can be finely adjusted by appropriately adjusting the ratio between the cyclic volatile methylsiloxane (b2) and the linear dimethylpolysiloxane / linear methylphenylpolysiloxane (b3).
　活性成分（親水性または親油性）が分散された状態で含まれる組成物（薬物分散型組成物）を調製する場合は、基剤（組成物から活性成分を除いたもの）は、前記シリコーン基剤のみでよく、他の基剤成分を使用しなくても調製可能であるが、必要に応じて色素、香料、顔料、酸化防止剤、紫外線吸収剤など、通常の皮膚用組成物に配合される成分を使用してもよい。薬物分散型の組成物を調製する場合、前記組成物に占めるシリコーン基剤の配合割合は、組成物の93重量％以上であることが好ましく、96重量％以上であることがより好ましく、98重量％以上であることが特に好ましい。 When preparing a composition (drug-dispersed composition) containing an active ingredient (hydrophilic or lipophilic) dispersed therein, the base (excluding the active ingredient from the composition) is the silicone group. It can be prepared without using other base ingredients, but it can be blended into normal skin compositions such as dyes, fragrances, pigments, antioxidants, and UV absorbers as necessary. Ingredients may be used. When preparing a drug-dispersed composition, the blending ratio of the silicone base in the composition is preferably 93% by weight or more, more preferably 96% by weight or more, and 98% by weight. % Or more is particularly preferable.
　活性成分（親油性）が溶解された状態で含まれる組成物（薬物溶解型組成物）を調節する場合は、親油性の活性成分を油性溶剤（非水性溶剤、油性基剤とも呼ばれる）で溶解し、シリコーン基剤と混和すればよい。この際、活性成分が溶解した油性溶剤は、シリコーン基剤に均一に混和するため、界面活性剤や、非シリコーン系の増粘剤（例えば、ワックスのようなペースト状又は固体状の炭化水素をベースとする増粘剤など）を用いなくても、薬物溶解型の組成物を得ることができる。非シリコーン系の増粘剤を用いると使用感が重くなり、界面活性剤を用いると安全性が悪くなるが、本願の組成物では、これらを含まなくても薬物溶解型の組成物を調製することができる。薬物溶解型の組成物を調製する場合、前記組成物に占めるシリコーン基剤の配合割合は、組成物の85重量％以上であることが好ましく、88重量％以上であることがより好ましく、93重量％以上であることが特に好ましい。 When adjusting a composition (drug-dissolving composition) that contains an active ingredient (lipophilic) dissolved, dissolve the lipophilic active ingredient in an oily solvent (also called non-aqueous solvent or oily base). And may be mixed with a silicone base. At this time, since the oily solvent in which the active ingredient is dissolved is uniformly mixed in the silicone base, a surfactant or a non-silicone thickener (for example, a paste-like or solid hydrocarbon such as wax is added. A drug-soluble composition can be obtained without using a base thickener or the like. When a non-silicone thickener is used, the feeling of use becomes heavy, and when a surfactant is used, safety is deteriorated. However, in the composition of the present application, a drug-dissolving composition is prepared even if these are not included. be able to. When preparing a drug-dissolving composition, the proportion of the silicone base in the composition is preferably 85% by weight or more, more preferably 88% by weight or more, and 93% by weight. % Or more is particularly preferable.
　前記親油性の活性成分を溶解するために使用される油性溶剤として、脂肪酸類、脂肪酸エステル類、高級アルコール類、炭化水素類等が挙げられる。特に好ましい油性溶剤は、セバシン酸ジエチル、セバシン酸ジイソプロピル、アジピン酸ジイソプロピル、中鎖脂肪酸トリグリセリド、プロピレングリコール脂肪酸エステル、トリイソオクタン酸グリセリン、イソステアリン酸、ヘキシルデカノール、オレイルアルコール、イソステアリルアルコール、オクチルドデカノール、パルミチン酸イソプロピル、ミリスチン酸イソプロピル、２－エチルヘキサン酸セチル、ミリスチン酸オクチルドデシル、イソステアリン酸ヘキサデシル、イソステアリルパルミテート、オレイン酸オレイル、精製ホホバ油、スクワラン、流動パラフィン、軽質流動パラフィンである。組成物中に占める油性溶剤の割合は１5重量％以下が好ましく、3～10重量％の範囲であることがより好ましい。 Examples of the oily solvent used for dissolving the lipophilic active ingredient include fatty acids, fatty acid esters, higher alcohols, hydrocarbons and the like. Particularly preferred oily solvents are diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, medium chain triglyceride, propylene glycol fatty acid ester, glycerin triisooctanoate, isostearic acid, hexyl decanol, oleyl alcohol, isostearyl alcohol, octyldodecanol, palmitic Isopropyl acid, isopropyl myristate, cetyl 2-ethylhexanoate, octyldodecyl myristate, hexadecyl isostearate, isostearyl palmitate, oleyl oleate, refined jojoba oil, squalane, liquid paraffin, light liquid paraffin. The proportion of the oily solvent in the composition is preferably 15% by weight or less, and more preferably in the range of 3 to 10% by weight.
　本発明に係る組成物は、無水の組成物であり、本質的に水を含まない。なお、本明細書中において「本質的に含まない」とは、意図的に組成物に添加していないことを意味し、不可避的に組成物に混入する場合のみ含むことを意味する。また、本発明に係る組成物は、水性成分（低級アルコールや多価アルコール等）も本質的に含まないか、または、少量のみ含む。即ち本発明に係る組成物は、水（不可避的に混入した場合にのみ含まれる。通常1重量％未満）と水性成分の合計量が、組成物の5重量％以下、好ましくは3重量％以下、より好ましくは1重量％以下の組成物であり、特に好ましくは、水を全く含まない組成物であり、さらに好ましくは水や水性成分を全く含まない組成物である。 The composition according to the present invention is an anhydrous composition and essentially does not contain water. In the present specification, “essentially not contained” means that it is not intentionally added to the composition, and means that it is inevitably included only when it is mixed into the composition. Further, the composition according to the present invention essentially does not contain an aqueous component (such as a lower alcohol or a polyhydric alcohol) or contains only a small amount. That is, the composition according to the present invention is contained only when it is inevitably mixed. Usually less than 1% by weight and the total amount of the aqueous component is 5% by weight or less, preferably 3% by weight or less of the composition. More preferably, it is a composition of 1% by weight or less, particularly preferably a composition containing no water, and more preferably a composition containing no water or an aqueous component.
　本発明に係る組成物の好ましい剤型として、軟膏剤様の油性ゲル剤からローション剤といった、ゲル状～液状を呈する剤型が挙げられる。 Favorable dosage forms of the composition according to the present invention include gel-to-liquid dosage forms such as ointment-like oily gels to lotions.
　本発明に係る組成物は、必要に応じて、色素、香料、顔料、酸化防止剤、紫外線吸収剤など、通常の皮膚用組成物に配合される成分を含有していてもよい。組成物中に占めるこれらの添加成分の割合は、10重量％以下が好ましく、3重量％以下がより好ましく、1重量％以下が特に好ましい。 The composition according to the present invention may contain components blended in a normal skin composition, such as a dye, a fragrance, a pigment, an antioxidant, and an ultraviolet absorber, if necessary. The proportion of these additive components in the composition is preferably 10% by weight or less, more preferably 3% by weight or less, and particularly preferably 1% by weight or less.
　なお、先行する段落において、本発明の組成物に使用される必須成分および任意成分の好ましい化合物名を記載してきたが、本発明の外用剤には、これらを任意に組み合わせて得られる組成物が含まれ、且つ、各成分について記載した濃度範囲を任意に組み合わせて得られる組成物も含まれる。また、先行する段落において記載した濃度、粘度等の数値範囲も任意に組み合わせ可能であり、数値範囲が複数記載されている場合、各数値範囲の上限値または下限値も任意に組み合わせ可能である。 In the preceding paragraphs, the names of preferred compounds of the essential components and optional components used in the composition of the present invention have been described. However, the external preparation of the present invention includes a composition obtained by arbitrarily combining these. Also included are compositions obtained by arbitrarily combining the concentration ranges described for each component. In addition, numerical ranges such as concentration and viscosity described in the preceding paragraph can be arbitrarily combined, and when a plurality of numerical ranges are described, an upper limit value or a lower limit value of each numerical range can be arbitrarily combined.
　本発明に係る組成物の製造方法の例を説明する。本発明に係る組成物が薬物分散型である場合は、（b1）と（b2）の予混合物に、（b3）を添加して攪拌することにより、もしくは、（b1）に、（b2）および（b3）を添加して攪拌することにより、（b1～b3）混合物を調製した後、活性成分をホモミキサーで分散させる方法が挙げられる。本発明に係る組成物が薬物溶解型である場合は、（b1）と（b2）の予混合物に、（b3）を添加して攪拌することにより、もしくは、（b1）に、（b2）および（b3）を添加して攪拌することにより、（b1～b3）混合物を調製した後、あらかじめ油性溶剤に溶解させた活性成分を撹拌混合させる方法が挙げられる。
　上記製造工程によって得られる組成物は、(b1)～(b3)の配合割合を調節することによって、半固形状～液状に調節することができる。より具体的には、（b2）及び／又は（b3）の量を少なくすることによって軟膏様の半固形状組成物とすることができ、（b2）及び／又は（b3）の量を多くすることによってローション状組成物とすることができる。 The example of the manufacturing method of the composition concerning this invention is demonstrated. When the composition according to the present invention is a drug-dispersed type, by adding (b3) to the premixed mixture of (b1) and (b2) and stirring, or (b1), (b2) and A method of preparing the mixture (b1 to b3) by adding (b3) and stirring and then dispersing the active ingredient with a homomixer can be mentioned. When the composition according to the present invention is a drug-dissolving type, by adding (b3) to the premixed mixture of (b1) and (b2) and stirring, or (b1), (b2) and There is a method in which (b1 to b3) mixture is prepared by adding (b3) and stirring, and then the active ingredient previously dissolved in an oily solvent is stirred and mixed.
The composition obtained by the above production process can be adjusted from semi-solid to liquid by adjusting the blending ratio of (b1) to (b3). More specifically, an ointment-like semi-solid composition can be obtained by reducing the amount of (b2) and / or (b3), and the amount of (b2) and / or (b3) is increased. Thus, a lotion-like composition can be obtained.
　以下、本発明を、実施例を用いてより詳細に説明するが、本発明は、実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the examples.
［実施例１］薬物分散型組成物の調製と評価
　表１・２に示す組成を有する組成物を、以下の手順によって調製した。なお、活性成分としては、ステロイド（ベタメタゾン酪酸エステルプロピオン酸エステル）及び活性型ＶD3（マキサカルシトール）を使用した。また、シリコーンエラストマー（b1）と環状揮発性メチルシロキサン[デカメチルシクロペンタシロキサン]（b2）の混合物として、ダウコーニング（DOW CORNING）社のST-Elastomer 10（シリコーンエラストマー：デカメチルシクロペンタシロキサン＝１２：８８［重量比］）を使用し、直鎖型ジメチルポリシロキサン（b3）として、ダウコーニング社のQ7-9120 Silicone Fluid 100CSTを使用した。 [Example 1] Preparation and evaluation of drug-dispersed composition A composition having the composition shown in Tables 1 and 2 was prepared by the following procedure. As active ingredients, steroids (betamethasone butyrate propionate) and activated VD 3 (maxacalcitol) were used. In addition, as a mixture of silicone elastomer (b1) and cyclic volatile methylsiloxane [decamethylcyclopentasiloxane] (b2), ST-Elastomer 10 (silicone elastomer: decamethylcyclopentasiloxane = 12 from DOW CORNING) : 88 [weight ratio]), and Q7-9120 Silicone Fluid 100CST of Dow Corning was used as the linear dimethylpolysiloxane (b3).
薬物分散型組成物の調製方法
（1）適切な容器に、（b1）と（b2）の混合物を秤取する。
（2）（1）に（b3）を添加し、混合する。
（3）（2）に、活性成分を添加し、室温下、ホモミキサーで（6000 rpm，5分間）撹拌し、分散させる。 Method for preparing drug-dispersed composition (1) Weigh the mixture of (b1) and (b2) into a suitable container.
(2) Add (b3) to (1) and mix.
(3) Add the active ingredient to (2) and stir with a homomixer (6000 rpm, 5 minutes) at room temperature to disperse.
　上記のようにして調製した組成物は、白色半透明のゲル状～液状の組成物であった。各組成物を顕微鏡で観察したところ、結晶の分散が確認され、薬物分散型組成物であることが確認された。 The composition prepared as described above was a white translucent gel-like liquid composition. When each composition was observed with a microscope, the dispersion of crystals was confirmed, and the composition was confirmed to be a drug-dispersed composition.
　上記各組成物について、適量を肌に塗布することにより、べたつきが少なく、滑らかな感触を有するか否かを基準として、各組成物の感触（手触り）を評価した。被験者は４名とし、各被験者が各組成物ごとに、感触が極めて良いものを◎、良いものを○、一般的なものを△、悪いものを×と評価し、４名の評価の平均を各組成物の評価とした。
　なお、表１・２に示す組成物は、シリコーンエラストマー(b1)の配合割合が大きいほど、高い粘度を示した。表の組成物のうち、No.007、No.009～No.011の組成物を低粘度用測定条件(条件１)で測定し、No.002の組成物を高粘度用測定条件(条件２)で測定した。
・条件１：B型粘度計(TBV-10H)、ローター：No.HH-12、回転数50rpm、測定時間10秒、測定温度25℃。
・条件２：B型粘度計(TBV-10H)、ローター：No.7、回転数20rpm、測定時間30秒、測定温度25℃
　結果を表１に示す。 About each said composition, the touch (hand) of each composition was evaluated on the basis of whether it had little smoothness and smooth touch by apply | coating an appropriate amount to skin. The number of subjects is four, and each subject is evaluated for each composition as ◎, ◯ for good, △ for general, × for poor, and × for the average of four subjects. Each composition was evaluated.
The compositions shown in Tables 1 and 2 showed higher viscosity as the blending ratio of the silicone elastomer (b1) was larger. Among the compositions in the table, the compositions No. 007 and No. 009 to No. 011 were measured under the measurement conditions for low viscosity (condition 1), and the composition No. 002 was measured under the measurement conditions for high viscosity (condition 2). ).
-Conditions 1: B type viscometer (TBV-10H), rotor: No. HH-12, rotation speed 50 rpm, measurement time 10 seconds, measurement temperature 25 ° C.
・ Condition 2: B-type viscometer (TBV-10H), Rotor: No. 7, Rotation speed 20rpm, Measurement time 30 seconds, Measurement temperature 25 ℃
The results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
［実施例２］薬物溶解型組成物の調製
　表３・４に示す組成を有する組成物を、以下の手順によって調製した。なお、活性成分、シリコーンエラストマー（b1）と環状揮発性メチルシロキサン[デカメチルシクロペンタシロキサン]（b2）の混合物、直鎖型ジメチルポリシロキサン（b3）は実施例１と同じものを使用し、セバシン酸ジエチルとしては、日光ケミカルズのNIKKOL DES-SPを使用した。 [Example 2] Preparation of drug-soluble composition A composition having the composition shown in Tables 3 and 4 was prepared by the following procedure. The active ingredient, a mixture of silicone elastomer (b1) and cyclic volatile methylsiloxane [decamethylcyclopentasiloxane] (b2), and linear dimethylpolysiloxane (b3) are the same as those used in Example 1, and sebacin NIKKOL DES-SP from Nikko Chemicals was used as the diethyl acid.
薬物溶解型組成物の調製方法
（1）適切な容器に、（b1）と（b2）の混合物を秤取する。
（2）（1）に（b3）を添加し、混合する。
（3）（2）に、あらかじめ油性溶剤に溶解させた活性成分を添加し、室温下、ホモミキサーで（6000 rpm，5分間）撹拌し、混和させる。 Method for preparing drug-dissolving composition (1) Weigh the mixture of (b1) and (b2) into a suitable container.
(2) Add (b3) to (1) and mix.
(3) Add the active ingredient previously dissolved in the oily solvent to (2), stir with a homomixer (6000 rpm, 5 minutes) at room temperature and mix.
　上記のようにして調製した組成物は、白色半透明のゲル～液状の組成物であった。各組成物を顕微鏡で観察したところ、結晶の分散は確認されず、薬物溶解型組成物であることが確認された。また、表３・４に示す組成物は、シリコーンエラストマー(b1)の配合割合が大きいほど、高い粘度を示した。上記各組成物について、実施例１と同じ方法により、感触（手触り）を評価し、No.102、No.105、No.107、No.108、No.111の組成物について粘度を測定した。No.105、No.107、No.108、No.111の組成物は上記条件１で測定し、No.102の組成物は上記条件２で測定した。結果を表３に示す。 The composition prepared as described above was a white translucent gel to liquid composition. When each composition was observed with a microscope, the dispersion of crystals was not confirmed, and it was confirmed to be a drug-dissolving composition. In addition, the compositions shown in Tables 3 and 4 showed higher viscosity as the blending ratio of the silicone elastomer (b1) was larger. About each said composition, the touch (hand) was evaluated by the same method as Example 1, and the viscosity was measured about the composition of No.102, No.105, No.107, No.108, No.111. The compositions of No. 105, No. 107, No. 108, and No. 111 were measured under the above condition 1, and the composition of No. 102 was measured under the above condition 2. The results are shown in Table 3.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　上記実施例から、本発明によれば、薬物分散型の場合も薬物溶解型の場合も、感触に優れた組成物を得ることができることが分かった。 From the above examples, it was found that according to the present invention, it is possible to obtain a composition having an excellent feel in both the drug dispersion type and the drug dissolution type.

Claims (9)

  1. 　無水の皮膚用組成物であって、
    （A）組成物の80重量％以上がシリコーン基剤であること、
    （B）前記シリコーン基剤が、
    　（b1）シリコーンエラストマー、
    　（b2）ケイ素原子数3～6の環状揮発性メチルシロキサン、および
    　（b3）直鎖型ジメチルポリシロキサン及び／又は直鎖型メチルフェニルポリシロキサン
    　を含んでなること、
    （C）組成物中に分散もしくは溶解した形態で存在する活性成分を含むこと、および
    （D）非シリコーン性増粘剤を含有しないこと
    を特徴とする皮膚用組成物。     An anhydrous skin composition comprising:
    (A) 80% by weight or more of the composition is a silicone base,
    (B) the silicone base is
    (B1) Silicone elastomer,
    (B2) comprising a cyclic volatile methylsiloxane having 3 to 6 silicon atoms, and (b3) a linear dimethylpolysiloxane and / or a linear methylphenylpolysiloxane,
    A skin composition characterized by comprising (C) an active ingredient present in a dispersed or dissolved form in the composition, and (D) not containing a non-silicone thickener.
  2. 　前記組成物の83重量％以上が前記シリコーン基剤であることを特徴とする、請求項１に記載の皮膚用組成物。 The dermatological composition according to claim 1, wherein 83% by weight or more of the composition is the silicone base.
  3. 　前記シリコーン基剤が（b1）～（b3）のみからなることを特徴とする、請求項１または２に記載の皮膚用組成物。 The skin composition according to claim 1 or 2, wherein the silicone base comprises only (b1) to (b3).
  4. 　前記活性成分を分散した形態で含むこと、および、前記組成物の93重量％以上が前記シリコーン基剤であることを特徴とする、請求項1～３のいずれかに記載の皮膚用組成物。 The skin composition according to any one of claims 1 to 3, wherein the active ingredient is contained in a dispersed form, and 93% by weight or more of the composition is the silicone base.
  5. 　前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝5.5～11.5：40～86：3～55（ただし、b1＋b2＋b3＝100）であること
    を特徴とする、請求項４に記載の皮膚用組成物。     The weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 5.5-11.5: 40-86: 3-55 (where b1 + b2 + b3 = 100), Item 5. A skin composition according to Item 4.
  6. 　前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝8～11.5：55～86：3～35（ただし、b1＋b2＋b3＝100）であること
    を特徴とする、請求項４または５に記載の皮膚用組成物。     The weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 8 to 11.5: 55 to 86: 3 to 35 (however, b1 + b2 + b3 = 100), Item 6. The skin composition according to Item 4 or 5.
  7. 　前記活性成分を溶解した形態で含むことを特徴とする、請求項1～３のいずれかに記載の皮膚用組成物。 The composition for skin according to any one of claims 1 to 3, comprising the active ingredient in a dissolved form.
  8. 　前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝10～11.5：73～85：3～17（ただし、b1＋b2＋b3＝100）であること
    を特徴とする請求項７に記載の皮膚用組成物。     The weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 10-11.5: 73-85: 3-17 (however, b1 + b2 + b3 = 100) 8. A composition for skin according to 7.
  9. 　前記シリコーン基剤における（b1）～（b3）の重量比率が、b1：b2：b3＝10.7～11.5：78～85：3～11.5（ただし、b1＋b2＋b3＝100）であること
    を特徴とする請求項７または８に記載の皮膚用組成物。     The weight ratio of (b1) to (b3) in the silicone base is b1: b2: b3 = 10.7-11.5: 78-85: 3-11.5 (however, b1 + b2 + b3 = 100) The composition for skin according to 7 or 8.
PCT/JP2012/083063 2011-12-21 2012-12-20 Composition for skin containing silicone base WO2013094683A1 (en)

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Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201636025A (en) * 2015-04-15 2016-10-16 Maruho Kk Pharmaceutical composition for skin
WO2017045196A1 (en) * 2015-09-18 2017-03-23 陆绮 Skin care composition containing polysiloxanes
ES2910987T3 (en) * 2016-08-09 2022-05-17 Univ Liverpool Ophthalmic compositions

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0940548A (en) * 1995-07-28 1997-02-10 L'oreal Sa Composition for dermatology or pharmacy and its preparation and its use
JPH09100211A (en) * 1995-06-01 1997-04-15 Unilever Nv Skin care composition containing dimethylimidasolidinon and retinol or retinyl ester
EP0915120A2 (en) 1997-11-05 1999-05-12 Dow Corning Corporation Method for termination of post cure in silicone elastomers
JP2001002555A (en) * 1999-06-24 2001-01-09 Shin Etsu Chem Co Ltd Skin cosmetic
JP2003501505A (en) * 1999-05-28 2003-01-14 ニュートロジーナ・コーポレイション Silicone gel containing salicylic acid
WO2003024413A1 (en) * 2001-09-14 2003-03-27 Shin-Etsu Chemical Co., Ltd. Composition and cosmetic preparation containing the same
JP2007530515A (en) 2004-03-22 2007-11-01 ガルデルマ リサーチ アンド デベロップメント Anhydrous pharmaceutical composition combining a siliconated agent and a dissolved active ingredient
JP2010520890A (en) * 2007-03-08 2010-06-17 バイオゾーン ラボラトリーズ，インコーポレイテッド Coating formulations that prevent and reduce scarring

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2725129B1 (en) * 1994-09-30 1997-06-13 Oreal WATER RESISTANT ANHYDROUS COSMETIC COMPOSITION
FR2779440A1 (en) * 1998-06-05 1999-12-10 Oreal Anhydrous composition with low viscosity, especially for cosmetic use
GB0216427D0 (en) * 2002-07-16 2002-08-21 Advanced Biotechnologies Inter Wound dressing
FR2871695B1 (en) * 2004-06-17 2008-07-04 Galderma Sa PHARMACEUTICAL COMPOSITION COMPRISING A SILICONE AGENT AND TWO SOLUBILIZED ACTIVE INGREDIENTS
US20060120979A1 (en) * 2004-12-02 2006-06-08 Joel Rubin Skin care composition comprising hydroquinone and a substantially anhydrous base
EP2356971B1 (en) * 2009-12-18 2016-04-20 Johnson & Johnson Consumer Inc. Compositions for repelling fluid and uses thereof

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09100211A (en) * 1995-06-01 1997-04-15 Unilever Nv Skin care composition containing dimethylimidasolidinon and retinol or retinyl ester
JPH0940548A (en) * 1995-07-28 1997-02-10 L'oreal Sa Composition for dermatology or pharmacy and its preparation and its use
EP0915120A2 (en) 1997-11-05 1999-05-12 Dow Corning Corporation Method for termination of post cure in silicone elastomers
US5929164A (en) 1997-11-05 1999-07-27 Dow Corning Corporation Quenching post cure
JPH11222556A (en) 1997-11-05 1999-08-17 Dow Corning Corp Method for stopping postcuring in silicone elastomer
JP2003501505A (en) * 1999-05-28 2003-01-14 ニュートロジーナ・コーポレイション Silicone gel containing salicylic acid
JP2001002555A (en) * 1999-06-24 2001-01-09 Shin Etsu Chem Co Ltd Skin cosmetic
WO2003024413A1 (en) * 2001-09-14 2003-03-27 Shin-Etsu Chemical Co., Ltd. Composition and cosmetic preparation containing the same
JP2007530515A (en) 2004-03-22 2007-11-01 ガルデルマ リサーチ アンド デベロップメント Anhydrous pharmaceutical composition combining a siliconated agent and a dissolved active ingredient
JP2010520890A (en) * 2007-03-08 2010-06-17 バイオゾーン ラボラトリーズ，インコーポレイテッド Coating formulations that prevent and reduce scarring

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US20140357729A1 (en) 2014-12-04

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